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Structural disorder promotes assembly of protein complexes.

Hegyi H, Schad E, Tompa P - BMC Struct. Biol. (2007)

Bottom Line: Using IUPred to predict the disorder for each complex, we found a statistically significant correlation between disorder and the number of proteins assembled into complexes.The predicted correlation is also supported by experimental evidence, by observing the structural disorder in protein components of complexes that can be found in the Protein Data Bank (median values 1. 5% for complexes of 2-4 components, and 9.6% for complexes of 11-100 components in yeast).Overall, it is suggested and discussed that the assembly of protein-protein complexes is enabled and probably promoted by protein disorder.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Budapest, Hungary. hegyi@enzim.hu

ABSTRACT

Background: The idea that the assembly of protein complexes is linked with protein disorder has been inferred from a few large complexes, such as the viral capsid or bacterial flagellar system, only. The relationship, which suggests that larger complexes have more disorder, has never been systematically tested. The recent high-throughput analyses of protein-protein interactions and protein complexes in the cell generated data that enable to address this issue by bioinformatic means.

Results: In this work we predicted structural disorder for both E. coli and S. cerevisiae, and correlated it with the size of complexes. Using IUPred to predict the disorder for each complex, we found a statistically significant correlation between disorder and the number of proteins assembled into complexes. The distribution of disorder has a median value of 10% in yeast for complexes of 2-4 components (6% in E. coli), but 18% for complexes in the size range of 11-100 proteins (12% in E. coli). The level of disorder as assessed for regions longer than 30 consecutive disordered residues shows an even stronger division between small and large complexes (median values about 4% for complexes of 2-4 components, but 12% for complexes of 11-100 components in yeast). The predicted correlation is also supported by experimental evidence, by observing the structural disorder in protein components of complexes that can be found in the Protein Data Bank (median values 1. 5% for complexes of 2-4 components, and 9.6% for complexes of 11-100 components in yeast). Further analysis shows that this correlation is not directly linked with the increased disorder in hub proteins, but reflects a genuine systemic property of the proteins that make up the complexes.

Conclusion: Overall, it is suggested and discussed that the assembly of protein-protein complexes is enabled and probably promoted by protein disorder.

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Distributions of complex-averaged disorder of long disordered regions for complexes of different sizes. The distributions are grouped by the sizes of complexes and singular proteins for which no evidence of complex-forming has been found. Magenta - singular proteins, cyan - complexes size 2-4, orange - complexes size 5-10, blue - complexes size 11-100. The average disorder for each complex has been calculated by predicting the individual protein components, and averaging them for each complex individually by considering only residues which fall into segments longer than 30 consecutive disordered residues. Complex averages were calculated and their % distributions are presented here. Medians are indicated in parentheses. A) E. coli complexes (significantly different distributions, p-value<0.001). B) Yeast complexes (significantly different distributions, p-value<0.001).
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Figure 3: Distributions of complex-averaged disorder of long disordered regions for complexes of different sizes. The distributions are grouped by the sizes of complexes and singular proteins for which no evidence of complex-forming has been found. Magenta - singular proteins, cyan - complexes size 2-4, orange - complexes size 5-10, blue - complexes size 11-100. The average disorder for each complex has been calculated by predicting the individual protein components, and averaging them for each complex individually by considering only residues which fall into segments longer than 30 consecutive disordered residues. Complex averages were calculated and their % distributions are presented here. Medians are indicated in parentheses. A) E. coli complexes (significantly different distributions, p-value<0.001). B) Yeast complexes (significantly different distributions, p-value<0.001).

Mentions: Regions of disorder of various lengths are conceptually distinguished in the literature, as the structural state of short disordered regions is more context-dependent, whereas that of long disordered regions is more context-independent. Whereas both kinds of regions are of clear functional significance, they may be involved in different kinds of functions [25,27-29]. Although not supported by comprehensive experimental evidence or theoretical considerations, the two classes are usually distinguished by a threshold length of about 30 amino acids, as also manifested in creating the predictor PONDR VSL2, which is composed of two separate predictors for short- and long disordered regions, based on this threshold value [28]. Because the assembly of large complexes is expected to depend more on such continuous sequences of disorder than on the average disorder of proteins, it is reasonable to ask if the presence of such regions correlates with the sizes of complexes. To this end, we determined the disorder of the complexes by taking into account only those stretches of amino acids that were predicted as disordered for at least 30 amino acids in an uninterrupted fashion. We got results similar to the previously described calculations (Figure 3) but the relative differences among the different groups are even more pronounced. For example, the median value more than triples upon going from the smallest (3.7% for complexes of 2–4 proteins) to the largest complexes (12.0% for complexes of 11–100 proteins) in the case of yeast.


Structural disorder promotes assembly of protein complexes.

Hegyi H, Schad E, Tompa P - BMC Struct. Biol. (2007)

Distributions of complex-averaged disorder of long disordered regions for complexes of different sizes. The distributions are grouped by the sizes of complexes and singular proteins for which no evidence of complex-forming has been found. Magenta - singular proteins, cyan - complexes size 2-4, orange - complexes size 5-10, blue - complexes size 11-100. The average disorder for each complex has been calculated by predicting the individual protein components, and averaging them for each complex individually by considering only residues which fall into segments longer than 30 consecutive disordered residues. Complex averages were calculated and their % distributions are presented here. Medians are indicated in parentheses. A) E. coli complexes (significantly different distributions, p-value<0.001). B) Yeast complexes (significantly different distributions, p-value<0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 3: Distributions of complex-averaged disorder of long disordered regions for complexes of different sizes. The distributions are grouped by the sizes of complexes and singular proteins for which no evidence of complex-forming has been found. Magenta - singular proteins, cyan - complexes size 2-4, orange - complexes size 5-10, blue - complexes size 11-100. The average disorder for each complex has been calculated by predicting the individual protein components, and averaging them for each complex individually by considering only residues which fall into segments longer than 30 consecutive disordered residues. Complex averages were calculated and their % distributions are presented here. Medians are indicated in parentheses. A) E. coli complexes (significantly different distributions, p-value<0.001). B) Yeast complexes (significantly different distributions, p-value<0.001).
Mentions: Regions of disorder of various lengths are conceptually distinguished in the literature, as the structural state of short disordered regions is more context-dependent, whereas that of long disordered regions is more context-independent. Whereas both kinds of regions are of clear functional significance, they may be involved in different kinds of functions [25,27-29]. Although not supported by comprehensive experimental evidence or theoretical considerations, the two classes are usually distinguished by a threshold length of about 30 amino acids, as also manifested in creating the predictor PONDR VSL2, which is composed of two separate predictors for short- and long disordered regions, based on this threshold value [28]. Because the assembly of large complexes is expected to depend more on such continuous sequences of disorder than on the average disorder of proteins, it is reasonable to ask if the presence of such regions correlates with the sizes of complexes. To this end, we determined the disorder of the complexes by taking into account only those stretches of amino acids that were predicted as disordered for at least 30 amino acids in an uninterrupted fashion. We got results similar to the previously described calculations (Figure 3) but the relative differences among the different groups are even more pronounced. For example, the median value more than triples upon going from the smallest (3.7% for complexes of 2–4 proteins) to the largest complexes (12.0% for complexes of 11–100 proteins) in the case of yeast.

Bottom Line: Using IUPred to predict the disorder for each complex, we found a statistically significant correlation between disorder and the number of proteins assembled into complexes.The predicted correlation is also supported by experimental evidence, by observing the structural disorder in protein components of complexes that can be found in the Protein Data Bank (median values 1. 5% for complexes of 2-4 components, and 9.6% for complexes of 11-100 components in yeast).Overall, it is suggested and discussed that the assembly of protein-protein complexes is enabled and probably promoted by protein disorder.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Budapest, Hungary. hegyi@enzim.hu

ABSTRACT

Background: The idea that the assembly of protein complexes is linked with protein disorder has been inferred from a few large complexes, such as the viral capsid or bacterial flagellar system, only. The relationship, which suggests that larger complexes have more disorder, has never been systematically tested. The recent high-throughput analyses of protein-protein interactions and protein complexes in the cell generated data that enable to address this issue by bioinformatic means.

Results: In this work we predicted structural disorder for both E. coli and S. cerevisiae, and correlated it with the size of complexes. Using IUPred to predict the disorder for each complex, we found a statistically significant correlation between disorder and the number of proteins assembled into complexes. The distribution of disorder has a median value of 10% in yeast for complexes of 2-4 components (6% in E. coli), but 18% for complexes in the size range of 11-100 proteins (12% in E. coli). The level of disorder as assessed for regions longer than 30 consecutive disordered residues shows an even stronger division between small and large complexes (median values about 4% for complexes of 2-4 components, but 12% for complexes of 11-100 components in yeast). The predicted correlation is also supported by experimental evidence, by observing the structural disorder in protein components of complexes that can be found in the Protein Data Bank (median values 1. 5% for complexes of 2-4 components, and 9.6% for complexes of 11-100 components in yeast). Further analysis shows that this correlation is not directly linked with the increased disorder in hub proteins, but reflects a genuine systemic property of the proteins that make up the complexes.

Conclusion: Overall, it is suggested and discussed that the assembly of protein-protein complexes is enabled and probably promoted by protein disorder.

Show MeSH